Difficile PCR Testing Research Articles

Impact of Clostridioides difficile Reporting on Antimicrobial Therapy Days Directed at Treatment of C. difficile Infections

Background: Previous studies have found that solely relying on molecular testing is likely to result in the overdiagnosis and overtreatment of C. difficile infections (CDI). Comparable outcomes have been demonstrated in patients with a positive molecular test (C. difficile PCR) result and a negative toxin immunoassay (C. difficile toxin) compared to patients without CDI by either testing Method: In 2021 Memorial Hermann Healthcare System converted from C. difficile PCR testing only to C. difficile PCR testing with reflex to C. difficile toxin if positive. A previous internal audit revealed that despite this change in testing, patients who were C. difficile PCR positive and C. difficile toxin negative were still receiving treatment. This study aimed to evaluate the impact of C. difficile reporting on the total days of therapy directed at the treatment of CDI of an 11-hospital health care system in patients who testing C. difficile PCR positive/C. difficile toxin negative. Methods: Pre-post, multicenter, retrospective, observational study conducted from January 1, 2023 through March 31, 2023 (pre-intervention) and July 1, 2023 through September 31, 2023 (post-intervention) which included hospitalized adult patients with a C. difficile test ordered within the study period. Intervention included a change in reporting of C. difficile PCR positive/C. difficile toxin negative results to display a laboratory comment. The comment notifies providers of the positive C. difficile PCR result while highlighting this probably reflects colonization with C. difficile as the C. difficile toxin is negative and treatment is rarely indicated. Results: In total, 989 C. difficile PCR were order in the pre-intervention cohort compared to 1009 in post-intervention. The overall rate of patients that received therapy directed at CDI decreased from 14% to 10% after the implementation of reporting change. Total days of therapy (DOT) also decreased by 29% from 482 to 342. Days of therapy that were administered to patients with C. difficile PCR positive/negative C. difficile toxin test decreased from 183 to 91. Conclusions: Adjusting the reporting of C. difficile results led to an overall numerical decrease of antimicrobial DOT directed at CDI treatment. In particular, among patients with a positive C. difficile PCR/C. difficile toxin negative test a 50% reduction in DOT was observed. Further data are required to assess the overall clinical impact of adjusting CDI reporting methods.

The Overuse of C. Difficile Testing Among Autologous Transplant Patients with Melphalan Conditioning: A Single Center Experience

Introduction: Melphalan is a common chemotherapy agent used as conditioning prior to autologous stem cell transplants (Auto SCT). Most frequent side effects are gastrointestinal (GI), with 91% of trial participants reporting symptoms. Among these complaints, diarrhea is the most common with a median onset of symptoms at 7 days and complaints lasting upwards of 17 days. Despite these known post-chemotherapy GI complications, transplant patients are often tested for Clostridium difficile ( C. difficile) given their immunocompromised status. Our study evaluated the rate of C. difficile testing in post-transplant patients to explore its utility and possible overuse in this population. Methods: During 2017-2022, patients who underwent Melphalan conditioning prior to Auto SCT were reviewed for C. difficile testing during transplant admission. We analyzed the timing and the results of C. difficile tests obtained during admission. All C. difficile tests obtained prior to admission or following discharge were excluded. From 2017-2020, a positive C. difficile test at our institution required only a positive C. difficile PCR test. Criteria for a positive C. difficile test changed beginning 2021, requiring both a positive C. difficle PCR and toxin antigen tests. Results: Of the 202 patients included in our database, 153 were tested for C. difficile during their transplant admission. 12/153 tests were positive (7.8%) with the average day of testing being 5.5 days post-transplant. Twelve patients were tested a second time during the same admission with the second test occurring on an average on day 12 post-transplant. All repeat tests were negative for C. difficile. All C. difficile tests following the implementation of the toxin assay resulted negative. Prior to the toxin assay, all positive PCR tests were treated with oral vancomycin. Conclusion: Our institutional data indicates that excessive C. difficile testing may occur in the setting of Melphalan conditioning. C. difficile testing was noted to be of low yield with positive rates in only 7.8% of patients. Furthermore, the positivity rate dropped to 0% among our cohort after implementation of the toxin assay in 2021. The mean cost of a single C. difficile test at our institution over 2017-2022 was $29.00 and this excessive testing leads to unnecessary financial burden incurred during the admission. Diarrhea occurring post-auto SCT in this population may be better explained as a side effect of Melphalan conditioning. Our data suggest it may be reasonable to withhold or delay testing until at or after day 7 post-transplant. In addition, repeat C. difficile testing within the same admission may be futile with all cases in our cohort resulting negative, further supporting our conclusion that excessive testing occurs in this population. We will further study our data as part of a targeted quality-improvement initiative to assess post-transplant outcomes with immediate versus deferred C. difficile testing.

Impact of mandatory nucleic acid amplification test (NAAT) testing approval on hospital-onset Clostridioides difficile infection (HO-CDI) rates: A diagnostic stewardship intervention.

Misclassification of Clostridioides difficile colonization as hospital-onset C. difficile infection (HO-CDI) can lead to unnecessary treatment of patients and substantial financial penalties for hospitals. We successfully implemented mandatory C. difficile PCR testing approval as a strategy to optimize testing, which was associated with a significant decline in the monthly incidence of HO-CDI rates and lowering of our standardized infection ratio to 0.77 (from 1.03) 18 months after this intervention. Approval request served as an educational opportunity to promote mindful testing and accurate diagnosis of HO-CDI.

Faecal microbiota transplantation for first or second Clostridioides difficile infection (EarlyFMT): a randomised, double-blind, placebo-controlled trial

Clostridioides difficile infection is an urgent antibiotic-associated health threat with few treatment options. Microbiota restoration with faecal microbiota transplantation is an effective treatment option for patients with multiple recurring episodes of C difficile. We compared the efficacy and safety of faecal microbiota transplantation compared with placebo after vancomycin for first or second C difficile infection. We did a randomised, double-blind, placebo-controlled trial (EarlyFMT) at a university hospital in Aarhus, Denmark. Eligible patients were aged 18 years or older with first or second C difficile infection (defined as ≥3 watery stools [Bristol stool chart score 6-7] per day and a positive C difficile PCR test). Patients were randomly assigned (1:1) to faecal microbiota transplantation or placebo administered on day 1 and between day 3 and 7, after they had received 125 mg oral vancomycin four times daily for 10 days. Randomisation was done by investigators using a computer-generated randomisation list provided by independent staff. Patients and investigators were masked to the treatment group. The primary endpoint was resolution of C difficile-associated diarrhoea (CDAD) 8 weeks after treatment. We followed up patients for 8 weeks or until recurrence. We planned to enrol 84 patients with a prespecified interim analysis after 42 patients. The primary outcome and safety outcomes were analysed in the intention-to-treat population, which included all randomly assigned patients. The trial is registered with ClinicalTrials.gov, NCT04885946. Between June 21, 2021, and April 1, 2022, we consecutively screened 86 patients, of whom 42 were randomly assigned to faecal microbiota transplantation (n=21) or placebo (n=21). The trial was stopped after the interim analysis done on April 7, 2022 for ethical reasons because a significantly lower rate of resolution was identified in the placebo group compared with the faecal microbiota transplantation group (Haybittle-Peto boundary limit p<0·001). 19 (90%; 95% CI 70-99) of 21 patients in the faecal microbiota transplantation group and seven (33%, 95% CI 15-57) of 21 patients in the placebo group had resolution of CDAD at week 8 (p=0·0003). The absolute risk reduction was 57% (95% CI 33-81). Overall, 204 adverse events occurred, with one or more adverse events being reported in 20 of 21 patients in the faecal microbiota transplantation group and all 21 patients in the placebo group. Diarrhoea (n=23 in the faecal microbiota transplantation group; n=14 in the placebo group) and abdominal pain (n=14 in the faecal microbiota transplantation group; n=11 in the placebo group) were the most common adverse events. Three serious adverse events possibly related to study treatment occurred (n=1 in the faecal microbiota transplantation group; n=2 in the placebo group), but no deaths or colectomies during the 8-week follow-up. In patients with first or second C difficile infection, first-line faecal microbiota transplantation is highly effective and superior to the standard of care vancomycin alone in achieving sustained resolution from C difficile. Innovation Fund Denmark.

Prospective audit and feedback of Clostridioides difficile PCR at the time of ordering increases appropriateness of testing

Background: Over-testing for Clostridioides difficile infection outside acute diarrheal illness without a clear alternative cause can lead to inappropriate diagnosis and treatment with antibiotic therapy. Preanalytical interventions such as education, order restriction, and electronic order assistance are common but are limited in effectiveness. As an alternative approach, our antibiotic stewardship program (ASP) implemented prospective audit and feedback (PAF) on C. difficile PCR orders to reduce inappropriate testing.Methods: The study was conducted at a 399-bed, tertiary-care, Veterans’ Affairs Medical Center and included adult inpatients and outpatients for whom C. difficile PCR testing was ordered. In the preintervention period from June through September 2019, the ASP was alerted to C. difficile PCR tests and collected data but did not intervene. From October 2019 to January 2020, the ASP performed real-time PAF at the time of ordering. Appropriateness of testing was determined based on whether there was a negative result in the prior 7 days and a 3-step review of clinical factors (Fig. 1). When possible, a direct conversation took place with the ordering provider. If not possible, a general note delineating appropriate clinical criteria for testing was generated. No PAF was done outside standard hours. The ASP recommended cancelling tests deemed inappropriate. Monthly test rates during the pre- and postintervention periods were compared using the Student t test with α = .05, and test appropriateness was compared using the χ2 test. All analyses were conducted using Microsoft Excel software. Results: During the preintervention period, a total of 418 tests were ordered (104.5 per month). This number decreased to 276 (69 per month) during the intervention period. (p Conclusions: Direct PAF at the time of C. difficile PCR ordering may increase test appropriateness and is associated with a reduction in overall testing, primarily by reducing the number of tests that are considered not appropriate on clinical grounds. PAF is effective but requires significant time investment by ASP staff and may not be a sustainable intervention over time.Funding: NoneDisclosures: None

Impact of Two-Step Testing Algorithm on Reducing Hospital-Onset Clostridioides difficile Infections

Clostridioides difficile infection (CDI) is one of the leading causes of hospital–onset infections. Clinically distinguishing true CDI versus colonization with C. difficile is challenging and often requires reliable and rapid molecular testing methods. At our academic center, we implemented a 2-step testing algorithm to help identify true CDI cases. The University of Mississippi Medical Center is a 700+ bed academic facility located in Jackson, Mississippi. Hospital-onset (HO) CDI was defined based on NHSN Laboratory Identified (LabID) event as the last positive C. difficile test result performed on a specimen using a multistep testing algorithm collected &gt;3 calendar days after admission to the facility. HO-CDI data were collected from all inpatient units except the NICU and newborn nursery. HO-CDI outcomes were assessed based on standardized infection ratio (SIR) data. In May 2020, we implemented a 2-step testing algorithm (Figure 1). All patients with diarrhea underwent C. difficile PCR testing. Those with positive C. difficile PCR test were reflexed to undergo enzyme immunoassay (EIA) glutamate dehydrogenase antigen (Ag) testing and toxin A and B testing. The final results were reported as colonization (C. difficile PCR+/EIA Ag+/Toxin A/B−) or true CDI case (C. difficile PCR+/EIA +/Toxin A/B +) or negative (C. difficile PCR−). All patients with colonization or true infection were placed under contact isolation precautions until diarrhea resolution for 48 hours. During the preintervention period (October 2019–April 2020), 25 HO-CDI cases were reported compared to 8 cases in the postintervention period (June 2020–December 2020). A reduction in CDI SIR occurred in the postintervention period (Q3 2020–Q4 2020, SIR 0.265) compared to preintervention period (Q4 2019–Q1 2020, SIR 0.338) (Figure 2). We successfully reduced our NHSN HO-CDI SIR below the national average after implementing a 2-step testing algorithm for CDI. The 2-step testing algorithm was useful for antimicrobial stewardship to guide appropriate CDI treatment for true cases and for infection prevention to continue isolation of infected and colonized cases to reduce the spread of C. difficile spores.Funding: NoDisclosures: None

IMPACT OF TIME-TO-TEST FOR CLOSTRIDIOIDES DIFFICILE INFECTION ON LENGTH OF STAY IN INFLAMMATORY BOWEL DISEASE PATIENTS HOSPITALIZED WITH FLARE

Guidelines recommend testing inflammatory bowel disease (IBD) patients hospitalized with flare for Clostridioides difficile infection (CDI), though little is known about whether a delay in testing for CDI is related to adverse outcomes. We examined the relationship between time-to-C. difficile PCR test order, collection, and result with adverse IBD outcomes.

IMPACT OF TIME-TO-TEST FOR CLOSTRIDIOIDES DIFFICILE INFECTION ON LENGTH OF STAY IN INFLAMMATORY BOWEL DISEASE PATIENTS HOSPITALIZED WITH FLARE

Abstract Background Guidelines recommend testing inflammatory bowel disease (IBD) patients hospitalized with flare for Clostridioides difficile infection (CDI), though little is known about whether a delay in testing for CDI is related to adverse outcomes. We examined the relationship between time-to-C. difficile PCR test order, collection, and result with adverse IBD outcomes. Methods We performed a retrospective cohort study of IBD patients hospitalized with flare through the emergency department (ED) between 2013 and 2020 at an urban academic medical center. The time from ED presentation to C. difficile test order (time-to-order), sample collection (time-to-collection), and test result (time-to-result) were collected. Time-to-result was stratified by within 6 hours, 6–24 hours, and 24 hours or longer. The primary outcome was length of stay (LOS). Secondary outcomes were inpatient anti-TNF administration and surgery. We used hemodynamic and laboratory values at presentation to evaluate disease severity as a confounding variable between length of stay and time-dependent variables. Results We identified 122 IBD patients hospitalized with flare. There were no significant differences in baseline characteristics among time-to-result groups. Despite a shorter time-to-result, the average LOS in the 6 hours group was 7.3 days, longer compared to the 6–24 hours group (4.3 days, p=0.018) and the 24 hours group (4.2 days, p=0.035; Table 1). There were no differences in inpatient anti-TNF administration (p=0.10) or surgery (p=0.08) among time-to-result groups. The markers of disease severity that correlated with longer LOS were C-reactive protein (CRP) (0.28 days, p=0.003), heart rate (0.478 days, p&amp;lt;0.001), diastolic hypotension (0.228 days, p=0.01), and hypoalbuminemia (0.215 days, p=0.02). Higher CRP correlated with earlier time-to-result (-0.218 hours, p=0.02). Patients with more markers of disease severity had earlier times-to-result (12.8 hours vs. 32.2 hours, p=0.014) and had a longer LOS (7.9 vs. 3.4 days, p=0.007) (Table 2). Patients with more severe disease had an earlier time-to-order (4.48 hours) compared to those with less severe disease (17.4 hours), though this difference did not meet statistical significance (p=0.09; Table 2). Conclusion Earlier time-to-result for CDI is associated with longer LOS in IBD patients hospitalized with flare. This inverse relationship is confounded by disease severity at presentation: patients with more severe disease have a shorter time-to-result and a longer LOS. It may be that these patients produce a stool sample more readily; however, the near significance of differences in time-to-order among severity groups suggest a role for provider bias, which must be studied further. Delay in testing was not associated with higher rates of inpatient anti-TNF administration or surgery.

786. Diagnostic stewardship of C difficile PCR testing with two step algorithm- A rural community hospital experience

BackgroundAn estimated 15% of hospitalized patients are asymptomatic carriers of C. diff. Inappropriate testing can lead to over diagnosis, treatment, isolation & substantial financial penalties. Ours is a rural 310 bed hospital with nurse driven C. diff test ordering protocol. Due to inadvertent test ordering, we had an uptick in the HO-CDI incidence with rates as high as 0.94 per 1000 patient days in 2017. In order to streamline testing, we initiated an infection preventionist(IP) led diagnostic stewardship program which was implemented in two phases in 2017-2019MethodsThe phase 1 involved daily review by IPs regarding the legitimacy of PCR order for minimum 3 loose stools in 24 hours, use of laxatives, presence of symptoms.There were concerns nationally that then CDI risk adjustment model from NHSN in 2017 does not optimally account for the impact of specific CDI testing methods used by individual hospitals on CDI SIRs. Hence, in Jan 2018 NHSN’s MDRO/CDI Protocol stated “Results of the final test that are placed in the patient’s medical record should be used to determine whether event meets the CDI LabID defn”.This led to phase 2 in mar 2019 which involved two step testing which started with C diff PCR assay with positive test reflexed to the toxin A/B assay.ResultsDuring the first phase, and a full year of the protocol in 2018, the number of completed PCR tests decreased to 626 (compared to 940 PCR tests in 2016) with an 34% decrease. In the year following implementation of the Diagnostic Stewardship, HO CDI decreased from 60 in 2017 to 43 events in 2018 with a reduction of 28%. Subsequently, HO CDI further decreased in 2019 to 28 with a reduction of 35%. Since the start of the project in 2017, HO CDI have decreased 54% in total. The reduction in 314 C diff PCR tests in the first year[2017-2018] led to a savings of $8300 in lab supplies. No readmissions with C difficile infection documented within 30 days on patients who did not meet the criterion for testing. Significant decrease in the usage of C difficile antibiotics. After the start of the two step test, we have seen a precipitous drop in our HO-CDI rates to less than 0.3 per 1000 pt days by the end of 2019.Quarterly comparison of HO CDI incidence for 2017-2020 HO CDI incidence before and following phase 1 and phase 2 interventions C. difficile antibiotic use trends during intervention period ConclusionIP run diagnostic stewardship programs with two step tests are highly successful in streamlining testing and in discriminating infection from colonizationDisclosures All Authors: No reported disclosures

Evaluating appropriateness and diagnostic stewardship opportunities of multiplex polymerase chain reaction gastrointestinal testing within a hospital system.

Objective:This single-center, retrospective, observational cohort study evaluates the appropriateness of the BioFire® FilmArray® Gastrointestinal (GI) multiplex PCR panel testing at a community-teaching hospital.Methods:All adult, hospitalized patients at Prisma Health Richland Hospital with a documented GI multiplex PCR panel from 1 April 2015 through 28 February 2018 were included in the analysis. Inappropriate use of the GI panel was defined as a test obtained without documented diarrhea, greater than 2 days of hospitalization, redundant use with other diagnostic tests (e.g. Clostridioides difficile PCR), or laxative use in the preceding 48 h. Antibiotic use and host variables were compared between groups with positive and negative results.Results:During the study period, 442 GI panels were obtained, among which 268 (61%) were deemed inappropriate. Primary reasons for inappropriate testing were lack of documented diarrhea (n = 92), greater than 2 days of hospitalization (n = 116), having a duplicate C. difficile PCR test ordered (n = 118), or laxative use in the 48 h before testing (n = 36). A total of 141 (32%) GI panels were positive. The most frequently identified pathogens were C. difficile (51.1%, n = 72), Enteropathogenic Escherichia coli (17.7%, n = 25), and Norovirus GI/GII (12.1%, n = 17). Patients with negative GI panel results were initiated on antibiotics significantly less frequently than those with positive GI panels (62.5% versus 80.2%, p < 0.00001).Conclusion:Stewardship opportunities exist to optimize the diagnostic application of the GI multiplex PCR panel.

1494. Clinical Factors Associated with a Positive C. difficile PCR Test

Background C. difficile infection (CDI) remains a significant cause of morbidity and mortality. The most appropriate clinical scenario for CDI testing is unclear. The IDSA/SHEA guideline recommends testing patients with unexplained new-onset ≥3 stools in 24 hours. This study sought to evaluate clinical factors associated with a positive C. difficile PCR test.MethodsWe conducted a retrospective cohort study of adults (age >18 years old) admitted to the University of Colorado Hospital for whom a C. difficile PCR, either as a standalone test or part of the Biofire® Filmarray® Gastrointestinal Panel (GI Panel), was ordered between October 1, 2015 and August 31, 2017. Data collected included time since admission to test order, hospital length of stay, history of CDI, antibiotic use in the past 90 days, clinical presentation in the 24 hours preceding test order (fever, leukocytosis, number of stools), and laxative or antibiotic administration within 24 hours of test order. Multivariate logistic regression was used to evaluate the association of the above variables with having a positive C. difficile PCR test. If multiple tests were ordered during a single hospital encounter, only the first test was included in our analysis.Results3,070 tests were performed; of these, 72% were ordered in the first 72 hours of admission. Overall, 19% of tests were positive. After adjusting for clinical variables, patients with a prior history of C. difficile or who had received antibiotics in the past 24 hours were significantly more likely to have a positive test [OR 2.2 95% CI (1.54, 3.18) P < 0.0001] and [OR 16 95% CI (8.22, 31.41) P < 0.0001], respectively. Patients who used laxatives were significantly less likely to have a positive test [OR 0.75 95% CI (0.61, 0.91) P = 0.004]. The number of stools and presence of fever or leukocytosis were not significantly associated with a positive test.ConclusionPrior history of C. difficile and antibiotics use was highly associated with a positive C. difficile test, while laxatives use was associated with a negative test. The number of stools was not significantly associated with a positive C. difficile test, suggesting this may be less important clinical factor than previously believed; however, restricting testing in patients receiving laxatives is likely warranted.Disclosures All authors: No reported disclosures.

2342. Elimination of Reflexive C. difficile PCR Testing Among Inpatients Resulted in Cost Savings Without Adverse Events

BackgroundDiagnosis of C. difficile infection is imperfect and various algorithms have been proposed. While PCR is sensitive for detecting toxin-carrying C. difficile, it leads to overdiagnoses resulting in antibiotic overuse and potentially unnecessary healthcare costs.MethodsWe performed a study of C. difficile cases after changing the testing protocol from reflexive vs. physician-requested PCR in cases of indeterminant EIA testing (antigen +, toxin −). The study was conducted among inpatient adults at four large hospitals in the southern California area and evaluated two 6-month periods: pre-intervention: (September 5, 2016–March 5, 2017) and post-intervention (3/6/2017–9/6/2017). Only the first C. difficile test during a period per patient was evaluated. Primary outcome was change in number of C. difficile diagnoses. Secondary outcomes included adverse events (missed cases of C. difficile and 30-day readmissions) and cost savings (accounting for PCR, isolation, and treatment costs).ResultsA total of 500 EIA indeterminant C. difficile test results were evaluated, 281 pre- and 219 post-intervention. There were no statistically significant differences in demographics, laboratory values (WBC, Cr), or hospital site between the study periods. A PCR was performed in 99.6% (280/281; one not performed due to an inhibitor) and 66% (144/219) in the pre- vs. post-intervention periods (P < 0.01); the PCR was positive in 65% (n = 182 and n = 94, respectively) in both periods. The change in testing strategy resulted in a 49% reduction in PCR testing and 48% fewer C. difficile cases. There were no differences between study periods in 30-day readmissions for all-cause (P = 0.96), GI-related illness (P = 0.93) or C. difficile (P = 0.47), nor in new or recurrent C. difficile cases (P > 0.99). No patient without a PCR and not treated was later diagnosed with C. difficile infection. Each reflexive PCR avoided led to a cost savings of $4,384/patient.ConclusionDiagnostic stewardship is an emerging area that can potentially reduce overdiagnosis and overtreatment of a variety of infectious diseases. Our study showed that changing C. difficile PCR testing among EIA-indeterminant cases from reflexive to requiring a physician order resulted in valuable cost savings without associated adverse events.Disclosures All authors: No reported disclosures.

2427. A Laboratory Simulation and Field Study of Simplified Qualitative and Quantitative Environmental Cultures for Clostridioides difficile

BackgroundReliable, simple methods to assess environmental contamination with Clostridioides difficile are needed for studies of terminal disinfection effectiveness and transmission of C. difficile from fomites. We compared two novel sampling methods for assessment of C. difficile contamination: (1) isopropanol wipe sampling with broth enrichment (IW), where alcohol wipes are used to sample surfaces followed by immersion in CDBB-TC broth and (2) ethanol-shock hand imprint sampling (HI), where surfaces are sampled by gloved hands moistened with ethanol hand sanitizer followed by imprinting hands on selective agar (CDBA-TC). Both methods allow for sampling of complex surfaces common in hospital environments.MethodsWe performed a laboratory simulation study using six 10-fold dilutions (101–106) of C. difficile spores from two strains sampled from fiberglass surfaces by IW and HI. We then performed a field study of 10 sites in 11 hospital rooms of patients with C. difficile infection (CDI) diagnosed < 48 hours prior to sampling. Results for the HI and IW method were quantitative and qualitative, respectively. We compared room contamination prevalence (total CFU per room by HI and sites positive/total sites per room) to the cycle crossing threshold (CT) from the diagnostic C. difficile PCR test (Cepheid) from the room occupant.ResultsThe IW laboratory limit of detection was 101 spores compared with 104 spores for HI. In the field study, IW and HI detected C. difficile contamination in 9/11 (82%) rooms at 22/110 (20%) sites and 5/11 (45%) rooms at 22/110 (20%) sites, respectively (Table 1). Six rooms with no detection by the HI method had a lower median number of sites positive per room compared with the 5 rooms with ≥1 cfu (1 vs 6, P < 0.05) (Table 1). The most commonly contaminated sites were linens (53%), call bells (43%), toilets (40%), blood pressure cuffs (40%), over-bed tables (38%), and bedrails (30%) (Table 2). Higher tcdB CT was associated with a lower total room contamination prevalence (Figures 1 and 2).ConclusionOur data suggest that the IW method is more sensitive for detection of C. difficile in the hospital environment, but the HI method offers quantitation. The prevalence of hospital room contamination for CDI patients appears to correspond with their toxin burden as estimated by PCR. Disclosures All authors: No reported disclosures.

2341. Effectiveness of Interventions Targeting Stewardship of Clostridium difficile Testing

Background Clostridium difficile infection (CDI) is the most common healthcare-associated infection. C. difficile PCR assays do not differentiate between colonization (seen in up to 21% of inpatients) and symptomatic disease, highlighting the importance of testing only symptomatic patients.MethodsInterventions included system-wide implementation of C. difficile testing guidelines, face-to-face education of licensed providers, and Best Practice Alerts (BPAs) embedded in the electronic health record (EHR) C. difficile PCR order. The guidelines recommend testing only when ≥ 3 liquid bowel movements within a 24-hour period, without laxatives, oral contrast or new enteral feeds in the preceding 24 hours, and without recent C. difficile PCR test (negative ≤ 7 days or positive < 30 days). We reviewed 100 consecutive C. difficile PCR orders across two hospitals pre- and post-intervention to assess compliance with guidelines; performed weekly review of all C. difficile PCRs, all BPA responses and all hospital-onset CDI. Cost savings were calculated based on published estimates of CDI attributable costs.ResultsHospital-onset CDI rates fell from 0.75 to 0.48 cases per 1000 patient-days, with an estimated costs savings of $259,555 per quarter and $1.04 million per year. There were no deaths due to CDI and no morbidity due to delayed CDI diagnosis. C. difficile PCR guideline compliance increased from 39% to 53%; orders decreased by 50% post-intervention. Receipt of laxatives and < 3 episodes of diarrhea were the most common reasons for guideline noncompliance. BPAs fired an average of 150 times/month. The most common trigger for BPA was laxative use. Providers canceled PCR orders in 40% of BPA events.ConclusionInterventions incorporating testing guidelines, face-to-face education, and EHR-embedded decision support resulted in fewer C. difficile PCRs orders, increased guideline compliance, lower rates of hospital-onset CDI and cost savings of $1 million per year without an increase in CDI-attributable death or morbidity.Disclosures All authors: No reported disclosures.

2637 An Unusual Cause of Persistent Abdominal Pain and Hematochezia an Adult Male; Small Bowel Meckel’s Diverticulum Causing Intussusception

INTRODUCTION: Symptomatic Meckel’s diverticulum (MD) in adults is extremely rare. The prevalence of MD in the entire population ranges from 0.3%–-2.9% with a lifetime incidence of symptoms at 4.2%. The common presentations of symptomatic MD are obstruction, gastrointestinal (GI) bleed, and inflammation; these complications are significantly more frequent in childhood. This case report highlights direct observation by traditional colonoscopy of small bowel MD as a lead point of intussusception in an adult. CASE DESCRIPTION/METHODS: A 25-year-old male presented to the hospital with acute on chronic periumbilical abdominal pain worsening over several days. He reported intermittent watery diarrhea and an episode of hematochezia. He was also hospitalized earlier in the year for bowel obstruction of unknown etiology, but found to have intussusception status-post diagnostic laparotomy and partial ileal resection. His vital signs were stable and the physical exam revealed peri-umbilical tenderness. Laboratory data resulted with fecal calprotectin 517.7 mg/kg, hemoglobin 10.2 g/DL, WBC 11.6 × 10exp9/L, ESR 33 mm/h, CRP 78.51 mg/L, and a negative Clostridium difficile PCR test. A CT abdomen/pelvis revealed mild thickening and mucosal hyperenhancement of the terminal ileum. A colonoscopy was performed due to concern for GI bleed and inflammatory bowel disease. On colonoscopy, the colon was normal, but a partially obstructing, mobile, villous mass was noted in the ileum. Subsequently, an exploratory laparotomy found recurrent small bowel intussusception. The ileal mass was resected and pathology showed ectopic gastric and pancreatic tissue confirming MD. An ulcer and acute inflammation were noted on the mass. His follow-up course was unremarkable and the patient’s symptoms have since improved. DISCUSSION: The symptoms of MD are significantly more common in other etiologies. In addition, symptomatic MD is rarely diagnosed in adulthood which makes the diagnosis of MD in adults a challenge. MD is often diagnosed by imaging modalities or direct observation during surgery. Balloon-assisted enteroscopy and capsule endoscopy are other diagnostic measures being explored. Endoscopy is indicated in patients presenting with GI bleed and was completed in this patient. A large portion of this patient’s distal ileum was previously resected and his altered anatomy allowed the direct observation of MD by colonoscopy. This case highlights a unique endoscopic finding that endoscopists should be aware as the etiology for GI bleed.

Effectiveness of a Two-Step Testing Algorithm for Reliable and Cost-Effective Detection of Clostridium difficile Infection in a Tertiary Care Hospital in Saudi Arabia.

The aim of this study was to evaluate the effectiveness of a two-step algorithm for the detection of Clostridium difficile infection. Setting and Design: A two-step testing algorithm was evaluated for testing stool samples from patients suspected of Clostridium difficile infection (CDI). A total of 103 stool specimens were tested using the C. diff Quik Chek Complete enzyme immunoassay (EIA) test and the Xpert C. difficile PCR test. A two-step algorithm was implemented, and data from 3518 patient samples tested during a two-year period after implementation were analyzed to evaluate the effectiveness. The sensitivity, specificity, and positive and negative predictive values (PPV, NPV) of the Quik Chek Complete EIA test were calculated using the Xpert C. difficile PCR test as a reference method. The sensitivity, specificity, PPV, and NPV of the Quik Chek Complete EIA test for C. difficile toxin were 46.7%, 100%, 100%, and 91%, respectively. The two-step algorithm, which combined the Quik Chek Complete EIA with Xpert C. difficile PCR, improved the sensitivity and also provided rapid detection. When algorithm-based testing was performed daily, there was a 66% reduction in turnaround time compared to batch testing using a lengthy ELISA procedure. Postimplementation data analysis showed that almost 89% of the samples could be reported immediately by initial screening with Quik Chek Complete EIA. Only 11% of the samples gave discrepant results and required PCR confirmation. According to our results, the two-step algorithm is an effective tool for the rapid and reliable detection of toxigenic C. difficile from stool samples.

529. Overdiagnosis of Clostridioides difficile with a Multiplex PCR Panel

BackgroundWhile advantageous by casting a wider diagnostic net, multiplex panels can be problematic if the pretest probability is low. A significant increase in reported Clostridioides difficile infections (CDI) was noted at our institution following introduction of a multiplex comprehensive GI (CGI) panel which includes an analyte for C. difficile. Owing to these concerns, the C. difficile analyte result was suppressed when reporting and providers were advised to order a standalone C. difficile PCR (CDPCR) test if CDI was a concern. The objective of this study was to investigate concerns of false positive C. difficile results from the CGI panel.Methods C. difficile diagnostic practices were prospectively evaluated from April to August 2017. Patient charts were reviewed in response to a positive C. difficile analyte on the CGI panel. CDPCR results were reviewed if ordered. If not ordered, chart review and discussion with the provider was conducted to investigate clinical suspicion for CDI. The results were analyzed to examine the performance of the C. difficile analyte on the CGI panel.ResultsOverall, a total of 1,611 CGI panels were performed with C. difficile being detected in 156 specimens. Of these positive results, a subanalysis was performed on 123 positive specimens for whom complete data was available. A CDPCR was performed in 80 (65%) of these specimens. Among those, only 44 (55%) were CDPCR positive and 22 (28%) were CDPCR negative (likely a false-positive CGI result), and 14 (17%) were rejected because of specimen consistency. For the remaining 43 C. difficile-positive CGI panel specimens that did not have an accompanying CDPCR, seven were in children below 2 years of age. Direct provider discussion occurred in the remaining 36 cases. Providers declined CDPCR testing in 24 of those cases due to a lack of clinical concern.ConclusionThe use of the CGI panel for C. difficile led to over diagnosis of CDI. This could have significant consequences for clinical care and the reporting of hospital acquired infections.Disclosures All authors: No reported disclosures.

481. Implementation of a Prospective, Pharmacist-Driven Clostridium difficile PCR Pre-Authorization Process to Optimize Appropriate Testing

BackgroundSince the implementation of more sensitive molecular diagnostics such as the Clostridium difficile PCR assay, hospitals have reported 50–100% increases in C. difficile infection (CDI) rates.MethodsThis single-center, quasi-experimental study assessed appropriateness of C. difficile PCR testing pre- and post-implementation of a prospective, pharmacist-led, pre-authorization process. The antimicrobial stewardship team prospectively reviewed all adult CDI-PCR cases sent to the laboratory prior to specimen processing twice daily, 7 days a week to assess for clinical appropriateness based on guideline criteria. Bone marrow transplant and pediatric patients were excluded. If a patient lacked appropriate CDI clinical criteria, the provider was contacted to discontinue the PCR. CDI-PCR appropriateness was assessed for all patients with a CDI-PCR during the preceding year as a retrospective, comparative cohort. The primary objective was to assess appropriateness of the CDI-PCR pre- and postintervention. Secondary objectives included intervention sensitivity, specificity, safety, total CDI-PCRs processed, and protocol adherence.ResultsA total of 714 patients were included (n = 360, preintervention; n = 354, postintervention). There were significantly more hospital-onset CDI cases and antimicrobial use within the past 30 days in the preintervention group [(248 vs. 133, respectively; P < 0.001) and (277 vs. 197, respectively; P < 0.0001)]. Appropriateness of the CDI-PCR significantly improved postintervention [n = 138 (38.3%) vs. n = 209 (59.1%), respectively; P < 0.001]. Prospective pharmacist intervention was required for 146 inappropriate CDI-PCRs resulting in 79 discontinued and 66 processed CDI-PCRs (n = 1 positive; n = 65 negative). No patient with a cancelled CDI-PCR required additional testing or escalation of care. When compared with the preintervention, the CDI-PCRs with pharmacist intervention demonstrated a significant increase in the sensitivity (64.7% vs. 98%; P < 0.0001) and decrease in specificity (66% vs. 48.3%; P = 0.015) with an improved NPV (91.9% vs. 99.3%; P = 0.035) and PPV (23.9% to 24.6%; P = 0.869).ConclusionImplementation of a pharmacist-led prospective CDI-PCR review improved PCR appropriateness and had no adverse clinical consequences although the PPV criteria remain low.Disclosures All authors: No reported disclosures.

Fecal calprotectin concentrations in cancer patients with Clostridium difficile infection.

Fecal calprotectin (fCPT) has been used as a surrogate marker for assessment of intestinal inflammation. We explore the utility of fCPT values as a diagnostic aid in cancer patients with suspected Clostridium difficile infection (CDI). A total of 232 stool specimens submitted for GeneXpert C. difficile PCR testing were included in the study. All specimens were tested for fCPT and toxin/GDH antigens. Clinical severity of CDI cases was determined by the IDSA/SHEA criteria. Significant differences of median fCPT values between CDI (n = 117, Median 183.6μg/g) and non-CDI (n = 115, 145.6μg/g, p = 0.006) patients were seen. In CDI patents, significantly lower fCPT values were found in patients with mild to moderate (n = 95, 182.1μg/g) than those with severe and severe to complicated (n = 22, 218.5μg/g, p = 0.014) scores, and among those that were toxin positive (n = 24, 200.2μg/g) vs. toxin negative (n = 86, 182.8μg/g, p = 0.044). Despite this overall trend, wide variations in fCPT values were found in all categories examined. A logistic regression analysis revealed that the fCPT values correlated independently with the severity of clinical manifestations (OR = 2.021, 95%CI = 1.132-3.608); however, it did not correlate with other clinical outcomes. Our study findings show that high fecal calprotectin levels correlate with toxin-positive and clinically severe CDI; however, wide variations in individual measurements preclude establishment of reliable cut-offs for routine diagnostic use in cancer patients.

Clinical Correlation of a Clostridium difficile Testing Algorithm Reflexing PCR Positive Specimens to Toxin Enzyme Immunoassay (EIA)

BackgroundAn algorithm promoted in the United Kingdom reflexes specimens positive for C. difficile by a nucleic acid amplification test (NAAT) to toxin EIA. Samples positive by NAAT and negative by toxin EIA are reported as “C. difficile could be present (ie, potential C. difficile excretor).” We explored the potential utility of this algorithm to distinguish C. difficile infection (CDI) from colonization compared with retrospective clinical assessment.MethodsLiquid stool specimens (n = 300) from inpatients (or the Emergency Department) submitted to the Cleveland Clinic Microbiology laboratory for C. difficile PCR testing (Cepheid Xpert C. difficile/Epi) with positive results were included in the study. The CDIFF QUICK CHEK COMPLETE GDH/toxin EIA assay (Alere) was performed according to manufacturer’s instructions. The charts of all patients were reviewed by Infectious Diseases physicians blinded to the EIA results. Using the American College of Gastroenterology (ACG) classification system, CDI status was determined to be mild, moderate, severe, or complicated. Patients without significant diarrhea (<3 unformed stools / 24 hours) were considered colonized. Those without documentation of stools were classified as indeterminate. Correlation of clinical assessment with EIA results was assessed.ResultsMost of the PCR positive specimens (75%) were toxin EIA negative. Correlation of clinical assessment with toxin EIA is summarized in the table below. Among patients colonized vs. those with CDI, the percentages with negative toxin EIA results were 80% and 73%, respectively. GDH antigen results were negative for 25 specimens—17 were from patients considered to have CDI. C. difficile PCR positive specimensClinical AssessmentToxin EIA positiveToxin EIA negative(No.)No.Row %No.Row %Indeterminate (11)19.01090.9Colonized (39)820.53179.5CDI (250)6726.818373.2Mild (47)1021.33778.7Moderate (68)2130.94769.1Severe (26)623.12076.9Complicated (109)3027.57972.5Total (300)7625.322474.7Conclusion Toxin EIA performed on samples positive for C. difficile by PCR does not reliably identify patients considered to have CDI with ACG criteria applied. GDH as an initial screen would not have detected 6.8% of patients with CDI.Disclosures S. S. Richter, bioMerieux: Investigator, Research support; BD Diagnostics: Investigator, Research support; Roche: Investigator, Research support; BioFire: Investigator, Research support; OpGen: Investigator, Research support